The Profile and Outcome of Snake-bite Envenomation in ...

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International Journal of Contemporary Medical Research Section: Medicine ISSN (Online): 2393-915X; (Print): 2454-7379 | ICV: 98.46 | Volume 7 | Issue 5 | May 2020

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The Profile and Outcome of Snake-bite Envenomation in Patients Admitted to a Rural Tertiary Care Hospital in South IndiaRinu Raju1, Asha Biju2, Anna Mathew3, Prakash Ramasami4

ORIGINAL RESEARCH

ABSTRACT

Introduction: There are 216 species of snakes in India, of which 52 species are poisonous. The most common highly venomous snakes are cobra (Najanaja), Russell’s viper (Dabiolarusselii), saw-scaled viper (Echiscarinatus) and the common krait (Bungaruscaeruleus). It is estimated that up to 20,000 people die annually in India from snake bites. Severity of symptoms is the traditional guideline used to estimate the anti-venom requirement. Study objectives were to assess the clinical profile of snake-bite envenomation, the predictors of severity and ASV usage in relation to outcomes in patients admitted with snake-bite envenomation to this rural tertiary care hospital in South India.Material and methods: This was a cross-sectional study of snakebite patients admitted to this tertiary care hospital from April 2008 to April 2017. The subjects were stratified into two groups based on outcome. The profile of snake-bite envenomation was detailed, including demographic details, snake-bite information, symptoms, treatment and hospitalisation. The severity was graded based on the traditional symptom-based grading and using the Snake-bite Severity Score (SSS). The number of vials of Anti Snake-bite Venom (ASV) administered were compared in relation to the outcome.Results: Snake bites are more common in summer but the mortality is greater in the monsoon season. Out of the 127 patients, 119 (93.7%) recovered and were discharged and 8 (6.3%) died in hospital. In the symptom-based grading all the patients with poor outcome were in grades 3 or 4. The SSS was above 8 in 29 (22.8%) patients, of whom 8 (27.6%) succumbed to the bite. The SSS is a good tool to predict outcome. Conclusion: The Snake-bite Severity Score is a validated tool for assessing the extent of envenomation and predicting patient outcomes following snake-bites. This study was planned to find out the clinical profile, symptomatology and predictors of severity and polyvalent anti snake venom (ASV) usage in relation to outcomes in patients with snake-bite envenomation.

Key words: Envenomation, Snake-bite Severity Score (SSS), Anti Snake Venom (ASV), Cobra, Krait, Viper.

INTRODCUTIONThere are about 236 species of snakes in India, most of which are non-poisonous. Their bites, apart from causing panic reaction and local injury, do not harm the patient. However, there are 13 known species that are poisonous and of these four, called the "Big Four", namely common cobra (Najanaja), Russell’s viper (Dabiolarusselii), saw-scaled viper (Echiscarinatus) and common krait

(Bungaruscaeruleus) are highly venomous and believed to be responsible for most of the poisonous bites in India.1,2

There are around 50,000 estimated snake bites every year in India though this may be underestimated because of lack of proper registration. The number of persons at risk of snakebite in our country during their lifetime is around 50 million people.3 In India, it is estimated that up to 20,000 people die annually from snake bites.4 Gautam et al found that children are usually more severely affected because of their smaller volume relative to venom dose and had a mortality of 13.3% in their study from Nepal.5

When a person is bitten by a poisonous snake, venom is injected, causing localized symptoms of mild pain and oedema and generalized ones including dyspnoea, ptosis, mental alteration, and tachycardia. In severe cases, patients develop acute renal failure, myocardial infarction, disseminated intravascular coagulation, and even death.6,7 In 2004, WHO established a snakebite Treatment Group, whose role was to develop recommendations to reduce mortality according to international norms. The protocol also includes categorizing the snakebite severity with the traditional snakebite severity scale based on symptomatology with a grade of 0 to 4. For grade 0, no anti venom is suggested. For grades 1 and 2, one vial (6,000 units) of anti-venom is recommended. For grade 3, 12,000 units are recommended, and for grade 4, 18,000 units. The group requiring additional administration of anti-venom showed a higher local effect score and a traditional snakebite severity grade at presentation, a shorter prothrombin and activated partial prothrombin time, a higher frequency of rhabdomyolysis and disseminated intravascular coagulopathy, and longer hospitalization than the group that did not need additional anti venom.8

The traditional snake-bite scale grades snake-bites with

1Interne, MOSC Medical College, Kolenchery, Kerala, 2Professor, Department of Medicine, MOSC Medical College, Kolenchery, Kerala, 3Professor, Department of Pharmacology, MOSC Medical College, Kolenchery, Kerala, 4Biostatistician, Consultant Biostatistician, Chennai, India

Corresponding author: Dr. Anna Mathew, Professor of Pharmacology, Professor, Department of Pharmacology, MOSC Medical College, Kolenchery, Kerala. 682311. India.

How to cite this article: Rinu Raju, Asha Biju, Anna Mathew, Prakash Ramasami. The profile and outcome of snake-bite envenomation in patients admitted to a rural tertiary care hospital in South India. International Journal of Contemporary Medical Research 2020;7(5):E1-E6.

DOI: http://dx.doi.org/10.21276/ijcmr.2020.7.5.4

Raju, et al. The Profile and Outcome of Snake-bite Envenomation

Section: Medicine International Journal of Contemporary Medical Research Volume 7 | Issue 5 | May 2020 | ICV: 98.46 | ISSN (Online): 2393-915X; (Print): 2454-7379

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no local or systemic signs or symptoms as Grade 0. Local swelling with absence of systemic sign, normal laboratory findings as Grade 1. Swelling extending past bite site (6–12 inch), ≥1 systemic sign or symptom or abnormal laboratory findings as Grade 2. Grade 3 includes snake-bites where there is marked swelling (>12 inch), tissue loss, multiple or severe systemic symptoms, immediate systemic signs, rapid progression of symptoms. The snake-bite is classified in Grade 4 when there is rapid development of local reaction, ecchymosis, necrosis, blebs, blisters, swelling severe enough to obstruct venous or arterial flow, swelling may involve ipsilateral trunk.9

Dart et al correlated the Snake-bite Severity Score (SSS) with the clinical assessment of physicians and found the SSS correlated well with the clinical condition of patients bitten by snakes. It provides a more objective instrument for the evaluation of severity and progression of envenomation in patients with snake-bite.10

The management of poisonous snake-bite envenomation includes supportive care and anti-snake-bite venom (ASV) administration. ASV is the only specific antidote to snake-bite envenomation in patients in whom the benefits outweigh the risks. Since ASV is relatively costly and often in limited supply, it should not be used indiscriminately. The risk of reactions should always be kept in mind. This study was planned to assess the clinical profile of snake-bite envenomation, the predictors of severity and ASV usage in relation to outcomes in patients admitted with snake-bite envenomation to this rural tertiary care hospital in South India.

MATERIAL AND METHODSAfter obtaining permission for this cross-sectional study, from the management and approval from the institutional review board and the ethics committee, the medical records of patients admitted to the intensive care of this tertiary care hospital with history of snake envenomation were consecutively accessed. All adult snake-bite patients over the age of 18 years admitted during the nine-year period were serially recruited to participate in the study. Relevant history, where the bite occurred, demographic data and clinical details were collected. Examination findings, included, bite-site description if the fang marks were visible and post-bite interval or the time elapsed after snake bite till the first dose of anti-snake-venom was given.Clinical evaluation of patient included examination of the local site of the bite and systemic examination of the patient. Bite site examination included signs and symptoms such as local pain, swelling, bite marks, lymphadenopathy. Systemic examination noted cardiovascular symptoms such as tachycardia and hypotension or bleeding tendencies; central nervous symptoms such as drowsiness, drooping of eyelid, dyspnoea with frothing, dysphasia, dysphagia, paresis of neck, jaw and body muscles leading to paralysis; respiratory failure and finally cardiac arrest.The sample size for single proportion was calculated with nMaster computer software using the prevalence in this area

of snakebite envenomation of 34% as recorded by Suchithra et al.11 The sample size for a confidence interval of 95% and precision of 8%, was found to be 135 patients with snakebite envenomation. All the patients were assessed using the traditional grading based on symptoms. We also graded the patients by the Snake-bite Severity Score, (Figure 1) which takes into consideration the local bite wound reactions, systemic symptoms and the haematological parameters such as prothrombin time (PT), partial thromboplastin time (PTT), international normalized ratio (INR) and activated partial thromboplastin time (a PTT). The dose of snake venom administered, the period of hospitalisation and the outcome were also noted. The participants were grouped based on the outcome of the illness into Group A- Good Outcome, including patients who recovered and were discharged well and group B-Poor Outcome, including patients who died in hospital. After searching all medical records, the data was entered into an Excel spread sheet, the frequencies, percentages and confidence limits were obtained for all variables and the data was summarised using tables, charts and graphs. As normality was present, the Chi square test was used to compare the categorical variables and the student t-test for continuous variables. A p value of <.05 was considered significant. The process of the study is detailed in the flow diagram in Figure 1

RESULTSIn this study we assessed the epidemiological and clinical profile of snake-bite envenomation in patients and compared the outcomes in relation to snakebite severity using the grading based on symptomatology and the snakebite severity score (SSS). The demographic characteristics of the patients are given in Table 1. Over three fourths of the patients admitted were male and over 60% of the patients were below 45 years of age. Only three patients were from an urban area while all the others were living in rural areas. Most of the patients were brought to hospital in less than 2 hours (78.7%).The details of the snake-bite in the good outcome group and the poor outcome groups are given in Table 2. The frequency of occurrence of renal, gastrointestinal, respiratory, central nervous system and cardiovascular system symptoms were significantly more in the poor outcome group. The frequency distribution of the systems affected is detailed in Table 3. The incidence of thrombocytopenia, leucocytosis, clotting time were significantly more in the poor outcome group.The signs and symptoms of envenomation were graded into four grades, in the traditional way based on the signs and symptoms. Grade 0 indicating minimal severity and grade 4 indicating maximal severity based on the signs and symptoms present. All the patients who died had a severity of Grade 3 or Grade 4. (Table 4)We also graded the severity of envenomation using the Snake-bite Severity Scale (SSS) into minimal envenomation

Raju, et al. The Profile and Outcome of Snake-bite Envenomation

International Journal of Contemporary Medical Research Section: Medicine ISSN (Online): 2393-915X; (Print): 2454-7379 | ICV: 98.46 | Volume 7 | Issue 5 | May 2020

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Demographic Variables Good outcomen = 119

Poor outcomen = 8

Totaln = 127

Gender MaleFemale

72 (60.5%) 47 (39.5%)

06 (75.0%)02 (25.0%)

78 (61.4%)49 (38.6%)

Age (years) 18-4445-65>65

59 (49.6%)51 (42.9%)09 (7.5%)

03 (37.5%)05 (62.5%)00 (0.00%)

62 (48.8%)56 (44.1%)9 (7.1%)

Place RuralUrban

116 (97.5%)03 (2.5%)

08 (100%)00 (0.00%)

124 (97.6%)03 (2.4%)

Time to Hospitalisation <2 hrs3-5 hrs6-24 hrs>24 hrs

96 (80.7%)15 (12.6%)06 (5.0%)02 (1.7%)

04 (50.0%)02 (25.0%)02 (25.0%)00 (0.00%)

100 (78.7%)17 (13.4%)08 (6.3%)02 (1.6%)

Outcome Discharged aliveDied in hospital

119 (100%)00 (0.00%)

00 (0.00%)08 (100%)

127 (100%)08 (6.3%)

Table-1: Baseline Characteristics of Study Participants

Details of Snake Bite Good outcomen = 119

Poor outcomen = 8

Totaln = 127

Snake identified CobraKraitViperNot identified

08 (6.7%)19 (16.0%)55 (46.2%)37 (31.1%)

00 (00.0%)00 (00.0%)05 (62.5%)03 (37.5%)

08 (.6.3%)19 (15.0%)60 (47.2%)40 (31.5%)

Snake-bite Scene Home RoadFieldOthers

47 (39.5%)19 (16.0%)44 (37.0%)09 (7.5%)

03 (37.5%)00 (0.0%)05 (62.5%)00 (0.0%)

50 (39.4%)19 (14.9%)49 (38.6%)09 (7.1%)

Snake-bite Season SummerMonsoonWinter

48 (40.3%)29 (24.4%)42 (35.3%)

03 (37.5%)05 (62.5%)00 (0.0%)

51 (40.1%)34 (26.8%)42 (33.1%)

Snake-bite Time Morning (04.01am - 8.00am)Day-time (08.01am - 04.00pm) Evening (04.01pm - 08.00pm) Night-time (08.01pm - 04.00am)

17 (14.3%)38 (31.9%)37 (31.1%)27 (22.7%)

0 (00.00%)4 (50.0%)4 (50.0%)0 (00.00%)

17 (13.4%)42 (33.1%)41 (32.3%)27 (21.3%)

Snakebite Site Upper limbLower limb/ Headneck

38 (31.9%)80 (67.2%)01 (0.8%)

01 (12.5%)07 (87.5%)00 (0.00%)

39 (30.7%)87 (68.5%)01 (0.8%)

Fang marks PresentAbsent

104 (87.4%)15 (12.6%)

6 (75.0%)2 (25.0%)

110 (86.6%)17 (13.4%)

Table-2: Details of Snake Bite of Study Participants

Signs and Symptoms Good outcomen = 119

Poor outcomen = 8

Totaln = 127

p value

Local reactions at bite site MildModerate Severe

38 (31.9%)61 (51.3%)20 (16.8%)

3 (37.5%)2 (25.0%)3 (37.5%)

41 (32.3%)63 (49.6%)23 (18.1%)

0.236

Gastro-intestinal disturbances MildModerate to severe

100 (84.0%)19 (16.0%)

5 (62.5%)3 (37.5%)

105 (82.7%)22 (17.3%)

0.252

Renal dysfunction MildModerate to severe

110 (92.4%)9 (7.6%)

1 (12.5%)7 (87.5%)

111 (87.4%)16 (12.6%)

0.000

Respiratory symptoms MildModerate to severe

113 (95.0%)6 (5.0%)

2 (25.0%)6 (75.0%)

115 (90.6%)12 (9.4%)

0.000

Central Nervous system signs MildModerate to severe

102 (85.7%)17 (14.3%)

2 (25.0%)6 (75.0%)

104 (81.9%)23 (18.1%)

0.000

Cardiovascular symptoms MildModerate to severe

111 (93.3%)8 (6.7%)

1 (12.5%)7 (87.5%)

112 (88.2%)15 (11.8%)

0.000

Thrombocytopenia PresentAbsent

01 (3.4%)118 (96.6%)

3 (9.4%)5 (90.6%)

4 (3.1%)123 (96.9%)

0.001

Leucocytosis PresentAbsent

09 (3.4%)110 (92.4%)

4 (50%)4 (50%)

13 (10.2%)114 (89.8%)

0.004

Clotting time prolongation PresentAbsent

17 (14.3%)102 (85.7%)

6 (75.0%)2 (25.0%)

23 (18.1%)104 (81.9%)

0.000

Table-3: Signs and Symptoms manifested after Snake-bite by Patients

Raju, et al. The Profile and Outcome of Snake-bite Envenomation

Section: Medicine International Journal of Contemporary Medical Research Volume 7 | Issue 5 | May 2020 | ICV: 98.46 | ISSN (Online): 2393-915X; (Print): 2454-7379

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Grading Good outcomen = 119

Poor outcomen = 8

Totaln = 127

p value

Based on Symptoms Grade 0Grade 1Grade 2Grade 3Grade 4

17 (14.3%)43 (36.1%)35 (29.4%)21 (17.6%)03 (2.5%)

00 (0.00%)00 (0.00%)00 (0.00%)03 (9.4%)05 (90.6%)

17 (13.4%)43 (33.9%)35 (27.6%)24 (18.9%)08 (6.3%)

0.000

Using the SSSMinimal envenomation (SSS <3)Moderate envenomation (SSS 4-7)Severe envenomation (SSS >8)

60 (50.4%)38 (31.9%)21 (17.6%)

00 (0.00%)00 (0.00%)08 (100%)

60 (47.2%)38 (29.9%)29 (22.8%)

0.000

Table-4: Severity of Snake-bite Envenomation based on Symptoms and with SSS

Figure-1: The study flow diagram based on strobe guidelines

Figure-2: Legend: 25 (19.6%) had a Snake-bite Severity Score (SSS) over 8 and needed more than 30 vials of Anti Snake-bite Venom (ASV). Of these severely envenomated patients, eight (6.3%) patients succumbed to the snake-bite.

Details of Snake Bite Good outcomen = 119

Poor outcomen = 8

Totaln = 127

p value

Ventilatory support ProvidedNot needed

04 (3.4%)115 (96.6 %)

08 (100 %)00 (0.00%)

12 (9.4 %)115 (90.6 %)

0.000

Initial use of anti-snake venom vials <5 vials5-10vials>10vials

66 (55.5 %)52 (43.7 %)01 (0.8 %)

05 (62.5 %)03 (37.5 %)00 (0.00%)

71 (55.9 %)55 (43.3 %)01 (0.8 %)

0.905

Total number of anti-snake venom vials <10 vials11-20 vials21-30 vial>30 vials

24 (20.2 %)45 (37.8 %)25 (21.0 %)25 (21.0 %)

00 (0.00%)03 (37.5 %)01 (12.5 %)04 (50 %)

24 (18.9 %)48 (40.3 %)26 (20.5 %)29 (22.8 %)

0.200

Duration of ICU stay <3 days4-7 days8-14 days

86 (72.3 %)31 (26.0 %)02 (1.7%)

04 (50 %)02 (25 %)02 (25 %)

90 (70.9 %)33 (26.0 %)04 (3.1 %)

0.001

Duration of hospital stay weeks <1 week1-2 weeks>2 weeks

91 (76.5 %)24 (20.2 %)04 (3. 3 %)

06 (75 %)02 (25 %)04 (50 %)

97 (81.5 %)26 (20.5 %)04 (3.1 %)

0.837

Table-5: Treatment and Outcomes of Snake-bite by Patients

(SSS <3), moderate envenomation (SSS 4-7) and severe envenomation (SSS>8) (Table 4)There was a significant difference between the good outcome group and the poor outcome with both the grading systems, however all the 8 patients who died were in the maximal envenomation group of 29 patients while with the traditional symptom-based grading the 8 who died were in Groups 3 and 4 consisting of 32 patients. Thus the SS is a little better

Raju, et al. The Profile and Outcome of Snake-bite Envenomation

International Journal of Contemporary Medical Research Section: Medicine ISSN (Online): 2393-915X; (Print): 2454-7379 | ICV: 98.46 | Volume 7 | Issue 5 | May 2020

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in predicting poor outcome.The treatment administered such as ventilatory support, number of vials of ASV given, length of intensive care unit stay and duration of hospitalisation of patients are given in Table 5.All the patients received an initial ASV dose of less than 10 vials. Of the 119 patients who recovered, 69 (58%) received less than 20 vials of ASV while all the patients who succumbed to the envenomation received more than 10 vials and half of them received more than 30 vials.All the 29 patients who had a score over 8 in the SSS and were classified as having maximal envenomation received over 30 vials of ASV. Of these 25 recovered and 4 succumbed to the bite. Of the remaining four, three received over 20 units and one received less than 20 vials of ASV.The SSS score and the number of ASV vials used are illustrated in Figure 2.

DISCUSSIONOf the 127 patients, admitted to the ICU in the past nine years with snake envenomation, 78 were males and 49 were females. Of the 127 snake-bites, 87 (68.5%) snakes could be identified and the remaining 40 snakes could not be identified. Snake-bites were more common in summer 51 (40.1%), however mortality was more when the bite occurred in the monsoon season. Over 40% of patients were bitten in summer, around 25% in the monsoon and 33% in the winter. All the patients who had a poor outcome were bitten in summer or the monsoon and five out of the eight who died were bitten during the monsoon season.There is a diurnal variation in snake-bites. Most of the bites occurred in the evening between 4.00 pm and 8.00 pm. Fewest bites occurred after 12.00 pm and before 4.00 am.There were four (3.15%) patients who required more than 8 days of intensive care unit stay and of these two (50%) patients died. Regarding outcomes for the 127 patients, 119 recovered and were discharged while 8 (6.3%) patients died in hospital. Of the eight who died, five (62.5%) patients were classified as Grade 4 by the severity grading based on symptomatology while all 8 (100%) fell into the category of maximal envenomation by the SSS categorisation. This shows that the SSS is a more reliable tool to predict outcome in patients of snake-bite envenomation. The common venomous snakes in this area are cobra, viper and krait.12 Of the 127 snake-bites, 87 (68.5%) were positively identified. The most common snake responsible for snake bites in this area was the viper 60 (47.2%).The evidence-based summary of signs and symptoms of snake bite, published after the Indian National Snakebite Conference is given below. 1. Local Pain/Tissue damage seen in cobra and viper but

not krait bites2. Ptosis/neurological signs seen with cobra and krait but

not viper3. Haemostatic abnormalities seen with viper bites not

cobra and krait bites.

4. Renal complications in Russel’s viper and hump-nosed viper but not cobra, krait and saw-scaled viper

5. Response to neostigmine is seen with cobra-bites but not for viper and krait bites.

6. Response to anti-snake venom in all except hump-nosed viper.12

In our study the renal, gastrointestinal, respiratory, central nervous system and cardiovascular system symptoms manifested were significantly more in the poor outcome group compared to those who recovered. The incidence of thrombocytopenia, leucocytosis, clotting time were significantly present in the patients who died compared to patients who were discharged from hospital. A review on snake-bites in South Asia says that mortality rates are highly variable, ranging from 0.5% to 58%. Most fatalities occur before reaching treatment centres.13 Studies from South India have reported mortality rates of 10.7% and 13.7%, while another similar study had a mortality rate of 3%.4,11,14 Our study shows a mortality rate of 6.3%.Traditionally, severity of envenomation is graded based on symptomatology into four grades to predict outcome and determine dose of ASV. Kang et al have raised the question if the traditional snakebite severity score correctly classifies envenomated patients and recommend measuring the pain and local effect and these are included in the SSS.14 In our study, of the eight patients who died 3 were in Grade 3 and five were in Grade 4. The SSS grades patients based on local reaction, symptomatology and coagulation parameters. All eight patients who died were in the maximal envenomation group showing that the SSS is a reliable and valid tool to predict outcome in snake-bite envenomation. (p=0.000). The snakebite protocol includes proper dressing, tetanus immunization, pain control, and elevation of the wounded part. The protocol also includes categorizing the snakebite severity to determine requirement of ASV. We found the Snake-bite Severity Score a valid and reliable tool of severity of envenomation which can predict outcome. All the patients in the poor outcome group had a Snake-bite Severity Score (SSS) over 8 and were classified in the maximal envenomation group (p=0.000). All patients with SSS over 8 received over 30 vials of polyvalent ASV. We found 69 (58%) of the 119 patients who recovered received less than 20 vials of ASV while 50 (42%) received over 20 vials of ASV. All the eight patients who succumbed to the envenomation (poor outcome group) received more than 10 vials and half of them received more than 30 vials.

CONCLUSIONThe mortality rate due to snake bite envenomation in our study was 6.3%. Mortality due to snake envenomation is greater in the monsoon months. Snake-bite Severity Score (SSS) is a good tool to predict patient outcomes in snakebite envenomation and to estimate anti-snake venom requirement.

ACKNOWLEDGEMENTSThe authors are grateful to the Dean, Management and

Raju, et al. The Profile and Outcome of Snake-bite Envenomation

Section: Medicine International Journal of Contemporary Medical Research Volume 7 | Issue 5 | May 2020 | ICV: 98.46 | ISSN (Online): 2393-915X; (Print): 2454-7379

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Research Department of the MOSC Medical College, Kolenchery for the encouragement and support provided to conduct this study. We are thankful to the Medicine department for making all the records available for us to do this study. We would also like to acknowledge Dr. C K Eapen, Pofessor Emeritus of Medicine, MOSC Medical College for the inspiration and guidance received.

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Source of Support: Nil; Conflict of Interest: None

Submitted: 23-03-2020; Accepted: 11-04-2020; Published: 09-05-2020